Safety device for a pre-filled syringe and an injection device

ABSTRACT

According to the invention, a safety device for a pre-filled syringe with an injection needle comprises of a support body adapted to mount the pre-filled syringe, a needle shield slidably arranged with respect to the support body, a retention and locking means (M) for retaining and locking the needle shield with respect to the support body in a first and a second advanced position (PA1, PA2) and in a retracted position (PR). The needle shield comprises an annular flange adapted to rest on the skin of the patient receiving an injection. The retention and locking means (M) are arranged at a distal end of the safety device.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 13/997,370, filed Jun. 24, 2013, which is a U.S. National PhaseApplication pursuant to 35 U.S.C. § 371 of International Application No.PCT/EP2011/074277 filed Dec. 30, 2011, which claims priority to EuropeanPatent Application No. 11150080.7 filed Jan. 4, 2011. The entiredisclosure contents of these applications are herewith incorporated byreference into the present application.

TECHNICAL FIELD

The present invention relates to safety devices that provide needlesafety and more particularly to safety devices for pre-filled syringes.The safety device is adapted to avoid accidental needle pricks andneedle injuries before, during and after an injection of a medicament ordrug contained in the pre-filled syringe. In particular, the safetydevice provides needle safety for a subcutaneous self-administratedinjection or for an injection administered by a health-careprofessional. The present invention further relates to injection devicescomprising pre-filled syringes.

BACKGROUND

Pre-filled syringes that are filled with a selected dosage of amedicament are well known injection devices for administering themedicament to a patient. Safety devices for covering a needle of apre-filled syringe before and after use are also well known. Typically,these devices comprise a needle shield that is either manually moved ormoved by the action of a relaxing spring to surround the needle.

A different type of safety devices known in the state of the art solvesthe object of providing needle safety by arranging the pre-filledsyringe movable relative to a body, whereas the pre-filled syringe isretracted into the body after the injection.

SUMMARY

Certain aspects of the present invention can provide an improved safetydevice for a pre-filled syringe.

Certain aspects of the invention can provide an improved injectiondevice comprising a pre-filled syringe that is safe to handle and inparticular prevents accidental needle stick injuries.

The aspects can be implemented by a safety device according to thepending claims.

Preferred embodiments of the invention are given in the dependentclaims.

In the context of this specification, the terms distal and proximal aredefined from the point of view of a person performing an injection.Consequently, a distal direction refers to a direction pointing towardsthe body of a patient receiving an injection and a distal end defines anend of an element that is directed towards the body of the patient.Respectively, the proximal end of an element or the proximal directionis directed away from the body of the patient receiving the injectionand opposite to the distal end or distal direction.

According to the invention, a safety device for a pre-filled syringewith an injection needle comprises

-   -   a support body adapted to mount the pre-filled syringe,    -   a needle shield slidably arranged with respect to the support        body,    -   a retention and locking means for retaining and locking the        needle shield with respect to the support body in a first and a        second advanced position and in a retracted position.

The needle shield comprises an annular flange adapted to rest on theskin of the patient receiving an injection. The retention and lockingmeans are arranged at a distal end of the safety device.

The needle shield and the support body are arranged so as to telescopewith respect to each other between three different positions, namely thefirst and second advanced position and the retracted position, so as tocover and to expose the injection needle of the pre-filled syringe thatmay be mounted within the support body of the safety device. Needlesafety is provided in at least the second position, so that accidentalneedle stick injuries may be prevented. In the retracted position, theinjection needle is exposed so as to allow for an insertion of theinjection needle into the skin of the patient receiving the injection.

The safety mechanism of the safety device can be viewed as an advancingmechanism that advances the needle shield to the second advancedposition after the injection is completed. Alternatively, the safetymechanism may be equivalently described as a retraction mechanism thatretracts the injection needle connected to the support body into theneedle shield after the injection is completed. The difference betweenthe retraction and the advancing mechanism originates from size of theneedle shield relative to the size of the support body. The larger partmay be deemed as being static during the telescoping movement of theneedle shield and the support body. Thus, a safety device within thescope of the present invention with a relative large support body may beviewed as comprising an advancing mechanism, whereas a safety devicewithin the scope of the present invention with a relative large needleshield may be seen as comprising an retraction mechanism.

The needle shield comprises an annular flange of increased surface thatis adapted to rest on the skin of the patient receiving the injection.The needle shield is axially translated between the first advancedposition and the retracted position by pushing the safety device againstthe skin of the patient, whereby the injection needle is inserted intothe skin. The safety device is particularly intuitive to operate.Furthermore, the needle shield may be made from an opaque material, sothat the injection needle is hidden from the view of the patient. Thismay help to reduce a possible patient's fear of needles and/orinjections.

The arrangement of the retention and locking means at the distal end ofthe safety device allows for a particularly compact design of the safetydevice. In particular, the length of the needle shield providing needlesafety for the injection needle of the pre-filled syringe retainedwithin and attached to the support body may be minimized. This savesmaterial costs in the manufacturing process of the safety device. Thesafety device may thus be economically mass-produced. Therefore, thesafety device is well suited as a disposable device that is only used ina single injection.

Preferably, the support body, the needle shield and/or the outer body isat least partially made from a transparent plastics material. Thesupport body, the needle shield and/or the outer body may either becompletely made from a transparent material or, alternatively, comprisewindows or sections that are made from a transparent material. Benefitsfor having multiple transparent components within the design includeaiding visual clarity of contents, reducing the size of the overallvisual appearance and adding accuracy to the needle insertion. Theretention and locking means are arranged at the distal end of the safetydevice, so that a view of a user is not obstructed. The content of thepre-filled syringe retained within the support body may be visible atall times. A dose of a medicament or drug is contained in an innercavity of the pre-filled syringe. The user may visually check thecontent of the pre-filled syringe throughout the injection.

The needle shield is movable from the first advanced position to theretracted position and further to the second advanced position. Theneedle shield in the first advanced position protrudes the support bodyin the distal direction by a first distance. Furthermore, the needleshield in the second advanced position protrudes the support body in thedistal direction by a second distance and surrounds the injection needleof the pre-filled syringe after the injection. The first distance issmaller than the second distance to indicate that the safety device hasbeen used.

The retaining and locking means are arranged to releasably retain theneedle shield in the first advanced position in a manner that isreleasable by a linear translatory movement of the needle shield withrespect to the support body parallel to a central axis of thesubstantially cylindrical safety device. The needle shield is simplypressed against the skin of a patient, whereby the needle shield slidesdistally and parallel to the central axis towards a retracted position.The distal movement releases the retention of the needle shield in thefirst advanced position and thus activates the safety mechanism of thesafety device that prevents accidental needle stick injuries after theinjection.

Preferably, the retention and locking means comprise at least onedeflectable resilient arm that provides a simple means for retaining theneedle shield in the first advanced position.

According to a possible embodiment of the invention, the resilient armis arranged with the needle shield as one piece. In particular, theresilient arm may be integrally moulded to the needle shield. The safetydevice comprises only a few parts preferably made from a plasticsmaterial and is inexpensive to manufacture. The resilient arm isarranged within the needle shield so as to prevent the resilient arm andthus the retention of the needle shield in the first, the second and orthe retracted position from being influenced from the exterior. Thisensures that the safety device works reliably and in particular hindersa person from tampering with the resilient arm locking the needle shieldin the second advanced position. Therefore, the safety device ispermanently prevented from being re-used after the injection has beencarried out.

The needle shield is preferably arranged as a double-walled shield,wherein the resilient arm is integrated to the inner wall to prevent theperson from tampering with the resilient arm.

The resilient arm latches to a catching recess formed into a distal endof the support body to releasably retain the needle shield in the firstadvanced position.

According to another possible embodiment of the invention, the resilientarm is pre-tensioned and deflected in the radial outward direction whenlatching to the catching recess to releasably retain the needle shieldin the first advanced position. The resilient arm is initially stressedand relaxes as soon as the needle shield is pushed with respect to thesupport body in the distal direction to release the needle shield.

The pre-tensioned resilient arm unbends due to a material memory effectwhen the needle shield is released from being retained in the firstadvanced position. In the unstressed state, the resilient armessentially extends parallel to the central axis of safety device, sothat the resilient arm is prevented from engaging the catching recessfor a second time. Upon release of the needle shield, the safetymechanism of the safety device is activated. The injection needle isautomatically shielded after the injection, whereby a re-use of thesafety device and/or the injection device is prevented. Thus, infectionsresulting from needle stick injuries with contaminated injection needlesmay be avoided.

According to yet another embodiment, the resilient arm is stressed andinwardly deflected when the needle shield is in the retracted and in thesecond advanced position. In this embodiment, the resilient arm isinitially in an unstressed state and is energized during use of thesafety device in an injection. This avoids a malfunctioning of thesafety device due to material fatigue after prolonged periods of storageof the safety device.

In particular, the retention and locking means of the safety device maycomprise a plurality of resilient arms that reliably retain the needleshield in various positions. According to a possible embodiment of theinvention, two of the stressed and inwardly deflected resilient arms arelocked to each other by interlocking elements of the retaining andlocking means arranged within the needle shield. The safety mechanism ofthe safety device has a compact design and may further be miniaturizedto be used in connection with needle tip safety device that are attachedto a hub mounting an injection needle or to a distal tip of a pre-filledsyringe.

In another embodiment, the resilient arms are made from a metal materialto overcome problems with material fatigue. Furthermore, resilient armsmade from the metal material may advantageously be miniaturized tosmaller length scales allowing for a compact design of the safety devicewithout compromising reliability.

Two inwardly deflected resilient arms that are arranged opposite to eachother may be locked to each other by two interjacent interlockingelements arranged opposite to each other. The two inwardly deflectedresilient arms and the two interlocking elements form an interlockedstructure that comprises an essentially ring-shaped cross-section. Thering-shaped interlocked structure comprises a reduced diameter thatensures that the released needle shield may move with respect to thesupport body without getting stuck or jammed. Furthermore, the compactdesign of this embodiment of the invention allows for a reduction ofmaterial and production costs.

The needle shield is biased with respect to the support body in thedistal direction by a spring means. The spring means provides an energysource to move the needle shield to the second advanced position. Aseparate interaction is not required from the user to provide needlesafety after the injection has been carried out.

According to yet another embodiment of the invention, the spring meanscomprises at least one spring arm made from a plastics material. Thespring arm provides an alternative spring means that is particularlyinexpensive mass-produced. The flexible spring arm is attached to theneedle shield and engages a first ramp formed to an outer surface of thesupport body, whereby the spring arm is deflected and stressed. Thedeflected and stressed spring arm biases the needle shield in the distaldirection. As the spring arm is stored in a unstressed state and isenergized during the injection, malfunctions resulting from materialfatigue is avoided.

According to the invention, an injection device comprises a safetydevice and a pre-filled syringe. The safety device comprises

-   -   a support body adapted to mount the pre-filled syringe,    -   a needle shield slidably arranged with respect to the support        body,    -   a retention and locking means for retaining and locking the        needle shield with respect to the support body in a first and a        second advanced position and in a retracted position.

The retention and locking means are arranged at a distal end of thesafety device. The injection device comprising the pre-filled syringeand the safety device combines the aforementioned advantages and avoidsinadvertent needle sticks injuries. The injection device is cheap tomanufacture and is disposed after a single injection has been carriedout.

The injection device is well suited to be used for self-administeredinjections and for injections performed by a health care professional.Consequently, the person referred to as the patient or the user may beone and the same person.

The pre-filled syringe may be filled with a medicament.

The term “medication”, or “drug”, or “medicament”, as used herein, meansa pharmaceutical formulation containing at least one pharmaceuticallyactive compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a protein, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exendin-3 or exendin-4 or an analogue or derivative ofexendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyhepta

decanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequence HHis-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 Exendin-4(1-39),

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDa) that are also knownas immunoglobulins which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and δ approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (CH) and the variable region (VH). In onespecies, the constant region is essentially identical in all antibodiesof the same isotype, but differs in antibodies of different isotypes.Heavy chains γ, α and δ have a constant region composed of three tandemIg domains, and a hinge region for added flexibility; heavy chains μ andε have a constant region composed of four immunoglobulin domains. Thevariable region of the heavy chain differs in antibodies produced bydifferent B cells, but is the same for all antibodies produced by asingle B cell or B cell clone. The variable region of each heavy chainis approximately 110 amino acids long and is composed of a single Igdomain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H—H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1 C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be better understood from the detaileddescription given in the following. The accompanying drawings are givenfor illustrative purposes only and do not limit the scope of the presentinvention.

FIG. 1 shows a perspective view of an injection device D according to afirst embodiment of the invention before use;

FIG. 2 shows a sectional view of the injection device D according to thefirst embodiment before use;

FIG. 3 shows a sectional view of the injection device D according to thefirst embodiment before a medicament is administered to a patient;

FIG. 4 shows a sectional view of the injection device D according to thefirst embodiment with a needle shield retracted in a retracted position;

FIG. 5 shows a sectional view of the injection device D according to thefirst embodiment after a medicament has been administered to thepatient;

FIGS. 6A and 6B show two different sectional views of the injectiondevice D according to the first embodiment after removal from theinjection site;

FIG. 7 shows a sectional view of the injection device D according to asecond embodiment before use;

FIG. 8A to 8E illustrate in detail the retention and locking meansarranged at the distal end of the safety device 1 according to the firstand second embodiment of the invention;

FIG. 9 shows a perspective view of an injection device D according to athird embodiment of the invention before use;

FIG. 10 shows a sectional view of the injection device D according tothe third embodiment before use;

FIGS. 11A and 11B show two cross-sections of the needle shield 1.1according to third embodiment of the invention;

FIG. 12 shows a sectional view of the injection device D according tothe third embodiment before the medicament is administered to a patient;

FIG. 13 shows the injection device D according to the third embodimentafter a medicament has been administered to the patient;

FIG. 14 shows the injection device D according to the third embodimentin a needle safe state;

FIG. 15 shows a sectional view of an injection device D according to aforth embodiment of the invention with the needle shield retained in theretracted position;

FIGS. 16A to 16D illustrate in detail the retention and locking meansaccording to the third and forth embodiment of the invention;

FIGS. 17A to 17D schematically illustrate possible arrangements of aresilient arm retaining the needle shield relative to the support body.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIG. 1 shows a perspective view of an injection device D with a safetydevice 1 for a pre-filled syringe 2 according to a first embodiment ofthe invention. The safety device 1 comprises a substantially cylindricaland hollow needle shield 1.1 with an annular flange 1.1.1 arranged at adistal end thereof. The needle shield 1.1 is arranged as a double walledshield with a substantially inner and outer wall. The annular flange1.1.1 projects radial outwards from the needle shield 1.1. and isadapted to rest on the skin of the patient during the injection. Edgesof the annular flange 1.1.1 are rounded for comfort and to avoidinjuries. The needle shield 1.1 is slidably arranged with respect to asupport body 1.2 that receives and mounts the pre-filled syringe 2.

Before usage of the safety device 1, the needle shield 1.1 is initiallyretained in a first advanced position PA1. The needle shield 1.1 in thefirst advanced position PA1 protrudes the support body 1.2 in a distaldirection by a first distance D1.

An annular bearing surface 1.2.1 is formed to the support body 1.2 thatprotrudes radial outwards. The annular bearing surface 1.2.1 limits thesliding movement of the needle shield 1.1 with respect to the supportbody 1.2 in the proximal direction.

The safety device 1 comprises an essentially cylindrical and hollowouter body 1.3 with an open distal and a closed proximal end. Theproximal end of the support body 1.2 is received within the open distalend of the outer body 1.3. The outer body 1.3 is slidably arranged withrespect to the support body 1.2 and may slide in a distal direction tosubstantially receive the support body 1.2 at the end of an injectionstroke.

A circumferential and outwardly protruding support flange 1.3.1 isintegrally formed to an outer surface of the outer body 1.3 close to itsdistal end. The outer body 1.3 is adapted to be gripped and pushed by auser in the distal direction, whereby the support flange 1.3.1 supportsthe hand of the user performing the injection stroke.

Preferably, the needle shield 1.1, the support body 1.2 and the outerbody 1.3 are made from a plastics material. The needle shield 1.1 may bemade from an opaque plastics material to hide an injection needle 2.1 ofthe pre-filled syringe 2 from the view of a patient throughout theinjection. This may help to ease a possible fear of needles of thepatient. Alternatively, the needle shield 1.1 may be made from atransparent plastics material, so that the user may visually confirm thecorrect placement of the injection needle 2.1 and easily insert theinjection needle 2.1 into the skin of the patient.

According to a possible embodiment of the invention, the support body1.2 is made from a transparent material, so that the content of thepre-filled syringe 2 received within the support body 1.2 is visible.The safety device 1 comprises retention and locking means M arranged atthe distal end of the safety device 1. Thus, the retention and lockingmeans do not obstruct the view of the user checking the content of thepre-filled syringe 2.

FIG. 2 shows a sectional view of the injection device D before use. Theinjection needle 2.1 of the pre-filled syringe 2 is covered by a needlecap 2.2 that engages a distal tip of a barrel 2.3. Preferably, theneedle cap 2.2 is at least partially made from a plastics material likerubber.

The pre-filled syringe 2 inserted into the support body 1.3 and attachedthereto by a mechanical connection engages a proximal barrel collar2.3.1 of the barrel 2.3.

An inner cavity 2.3.2 of the pre-filled syringe 2 contains a dose of amedicament or drug. A stopper 2.4 that is connected to a plunger 2.5fluid-tightly seals a proximal end of the inner cavity 2.3.2. Thestopper 2.4 may be moved by pushing the plunger 2.5 in the distaldirection to expel the dose of the medicament through the injectionneedle 2.1. The plunger 2.5 is attached to or abuts an inner surface ofthe outer body 1.3, so that the plunger 2.5 and the stopper 2.4connected thereto may be moved by pushing the outer body 1.3 withrespect to the support body 1.2 in the distal direction.

A spring means 1.4 is arranged within the needle shield 1.1 and biasesthe needle shield 1.1 with respect to the support body 1.2 in the distaldirection. According to the first embodiment of the invention, thespring means 1.4 is designed as a compression spring made from a metal.Alternatively, the spring means 1.4 may comprise other suitable means tobias the needle shield 1.1, like, for example, a torsion spring orresiliently deflectable spring arms made from suitable plasticsmaterials.

The retention and locking means M that releasable retain the needleshield 1.1 in the first advanced position PA1 are arranged at the distalend of the safety device 1. The retention and locking means M comprise acatch 1.2.2 formed to an outer surface of the support body 1.2 andprotruding therefrom in a radial outward direction to engage the needleshield 1.1.

FIG. 3 shows a sectional view of the injection device D after removal ofthe needle cap 2.2. The retention and locking means M comprise tworesilient arms 1.1.2 integrally moulded to the needle shield 1.1 andarranged opposite to each other. The resilient arm 1.1.2 is arrangedwithin the needle shield 1.1 to shield the resilient arm 1.1.2 fromexterior influences. In particular, the arrangement of the resilient arm1.1.2 prevents a person from tampering with the resilient arm 1.1.2retaining and locking the needle shield 1.1 in various positions. Withcross-reference to FIG. 8A, it can be seen that the resilient arms 1.1.2are radial outwardly deflected and in the pre-tensioned state. Theresilient arms 1.1.2 latch to a catching recess 1.2.3 formed into thedistal end of the support body 1.2 to releasably retain the needleshield 1.1 in the first advanced position PA1. The mechanical connectionbetween the outwardly flexing resilient arm 1.1.2 and the catchingrecess 1.2.3 may be released by a linear translatory of movement of theneedle shield 1.1 with respect to the support body 1.2 parallel to acentral axis A of the substantially cylindrical safety device 1, wherebythe deflected resilient arm 1.1.2 unbends due to a material memoryeffect.

FIG. 4 shows a sectional view of the injection device D before aninjection stroke is performed by the user. The needle shield 1.1 islocated in a retracted position PR and bears against the annular bearingsurface 1.2.1 in the proximal direction. The injection needle 2.1 of thepre-filled syringe 2 protrudes the annular flange 1.1.1 of the needleshield 1.1 in the distal direction. The spring means 1.4 designed as thecompression spring is fully compressed and stressed.

An outward projection 1.2.4 is formed to a proximal end of the supportbody 1.2 that protrudes radial outwards into a longitudinal recess 1.3.2formed into an inner surface of the outer body 1.3. Preferably, twooutward projections 1.2.4 are formed to opposite sides of the supportbody 1.2 that are received within respective longitudinal recesses 1.3.2of the outer body. The longitudinal recess 1.3.2 extends parallel to thecentral axis A and over a substantial axial length of the outer body1.3. The outward projection 1.2.4 travels within the longitudinal recess1.3.2 when the outer body 1.3 is slid with respect to the support body1.2 to expel the dose of the medicament contained in the pre-filledsyringe 2 through the injection needle 2.1. This avoids a relativerotation between the outer body 1.3 and the support body 1.2 during theinjection, so that a jamming of these parts 1.2, 1.3 may be prevented.

Furthermore, a first inward projection 1.3.3 is located at the distalend of the longitudinal recess 1.3.2 that abuts the outward projection1.2.4 of the support body 1.2. The outward projection 1.2.4 has toovercome the first inward projection 1.3.3 before the outer body 1.3 maytravel with respect to the support body 1.2 in the distal direction. Theinteraction between the inward and outward projection 1.3.3, 1.2.4generates a resistive force that is larger than a respective requiredforce required to move the needle shield 1.1 from the first advancedposition PA1 to the retracted position PR. This ensures that the needleshield 1.1 is in the retracted position PR and the injection needle 2.1is inserted into the skin of the patient before the outer body 1.3 ispushed distally. Thus, so-called wet injections and a spilling of themedicament before the injection needle 2.1 is inserted into the skin ofthe patient are avoided.

FIG. 5 shows a sectional view of the injection device D at the end ofthe injection stroke. The stopper 2.4 connected to the plunger 2.5 isfully depressed into the inner cavity 2.3.1 of the pre-filled syringe 2.The support body 1.2 is substantially received within the hollow outerbody 1.3.

The resilient arm 1.1.2 of the retention and locking means M is in amechanical unstressed state and extends essentially parallel to thecentral axis A of the safety device 1.

FIGS. 6A and 6B show two different sectional views of the injectiondevice D after removal from the injection site. The sectional planeshown in FIG. 6A extends perpendicularly to the one shown in FIG. 6B.The needle shield 1.1 is located in a second advanced position PA2 andsurrounds the injection needle 2.1 after the injection.

As shown in FIG. 6A, the resilient arm 1.1.2 extends parallel to thecentral axis A, so that a second engagement of the resilient arm 1.1.2with the catching recess 1.2.3 is avoided. The resilient arm 1.1.2 maythus pass beyond the catching recess 1.2.3, so that the needle shield1.1 in the second advanced position PA2 protrudes the support body 1.2by a second distance D2 that exceeds the first distance D1.

The needle shield 1.1 is locked to the second advanced position PA2 sothat a subsequent exposure of the injection needle 2.1 is prevented. Asshown in FIG. 6B, the catch 1.2.2 of the support body 1.2 abuts a secondinward projection 1.2.5 formed to an inner surface of the needle shield1.1 to prevent a proximal movement of the needle shield 1.1 with respectto the support body 1.2.

FIG. 7 shows a sectional view of an injection device D according to asecond embodiment of the invention in a packaged state before theinjection device D is used to administer the dose of the medicamentcontained in the pre-filled syringe 2 to the patient.

The safety device 1 according to the second embodiment of the inventionis similar to the one of the first embodiment in both functionality anddesign. A needle shield 1.1 of the second embodiment comprises compactdimensions and covers, compared to the needle shield 1.1 of the firstembodiment, only a relative small area of the support body 1.2 whenarranged in the first advanced position PA1, the second advancedposition PA2 or the retracted position PR. In particular when thepre-filled syringe 2 is retained in the support body 1.2 made from atransparent material, the user may clearly view the content of thepre-filled syringe 2 independent of the positioning of the needle shield1.1.

The retention and locking means M of the safety device 1 according tothe second embodiment of the invention work similar to the retention andlocking means M of the first embodiment described before.

FIG. 8A to 8E illustrate in detail the safety mechanism and theretention and locking means arranged at the distal end of the safetydevice 1 according to the first and second embodiment of the invention.

A possible sequence of actions for administering the dose of themedicament to the patient with the injection device D according to thefirst and second embodiment of the invention is described in thefollowing:

After removal of the needle cap 2.2 from the distal tip of the barrel2.3, the injection device D is arranged at the injection site, so thatthe annular flange 1.1.1 rests onto the skin of the patient. The needleshroud 1.1 is retained in the first advanced position PA1, wherein, asillustrated in FIG. 8A, the needle shroud 1.1 projects from the distalend of the support body 1.2 by the first distance D1. The outer body 1.3is gripped by the user performing the injection and pushed distallytowards the skin surface. As a distal movement of the outer body 1.3with respect to the support body 1.2 is initially prevented by theinteraction of outward projection 1.2.4 with the first inward projection1.3.3, the needle shield 1.1 is released from the first advancedposition and pushed in the proximal direction, as illustrated in FIGS.8A and 8B. The outwardly deflected resilient arms 1.1.2 disengage thecatching recesses 1.2.3 and unbend due to a material memory effect. Theresilient arm 1.1.2 now extends straight and substantially parallel tothe central axis A of the safety device 1.

As illustrated in FIG. 8C, the needle shield 1.1 is moved further in theproximal direction towards the retracted position PR shown in FIG. 8D,whereby the injection needle 2.1 is inserted into the skin of thepatient.

After the needle shield 1.1 reached the retracted position PR pushingthe outer body 1.3 in the distal direction causes the outward projection1.2.4 to overcome the first inward projection 1.3.3, whereby the outerbody 1.3 is released, so that the outer body 1.3 may move in the distaldirection. Simultaneously, the stopper 2.4 connected to the outer body1.3 via the plunger 2.5 depresses into the inner cavity 2.3.2, wherebythe dose of the medicament contained in the inner cavity 2.3.2 isexpelled through the injection needle 2.1 and disposed beneath the skinof the patient.

When the stopper 2.4 is fully depressed into the inner cavity 2.3.2, theinjection device D is removed from the injection site. The spring means1.4 relax and move the needle shroud 1.1 to the second advanced positionPA2 shown in FIG. 8E. The resilient arm 1.1.2 passes beyond the catchingrecess 1.2.3, so that the needle shroud 1.1 projects from the supportbody 1.2 by the second distance D2 that is larger than the firstdistance D1.

Even if the injection is aborted before the stopper 2.4 reaches thedistal end of the inner cavity 2.3.2 and the medicament is onlypartially administered, needle safety is still provided upon removal ofthe injection device D from the injection site. The needle shield 1.1 isdriven to the second position PA2 shown in FIG. 8E to cover theinjection needle 2.1 after the medication has been partially delivered.

FIG. 9 shows an injection device D according to a third embodiment ofthe invention in a perspective view before use. The needle shield 1.1 ofthe third embodiment is biased in the distal direction by spring means1.4 that comprise a plurality of spring arms 1.4.1 made from a resilientplastics material. A plurality of longitudinal apertures 1.1.3corresponding to the spring arms 1.4.1 are formed into the needle shield1.1. The longitudinal aperture 1.1.3 allows for a deflection of thespring arm 1.4.1 in the radial outward direction.

FIG. 10 shows a sectional view of the injection device D according tothe third embodiment before use. The spring arms 1.4.1 are attached to adistal end of the needle shield 1.1. A proximal end of the spring arm1.4.1 engages a first ramp 1.2.6 formed to the outer surface of thesupport body 1.2. During the injection, the proximal end of the springarm 1.4.1 travels along the first ramp 1.2.6, whereby the spring arm1.4.1 is deflected outwardly and stressed to bias the needle shield 1.1with respect to the support body 1.2 in the distal direction.

The resilient arm 1.1.2 of the retention and locking means M latches tothe catching recess 1.2.3 to releasably retain the needle shield 1.1 inthe first advanced position PA1. The resilient arm 1.1.2 is notpre-tensioned and extends essentially parallel to the central axis A ofthe safety device 1. A second ramp 1.2.7 is formed to the distal end ofthe support body 1.2 that engages and deflects the resilient arm 1.1.2in the radial inward direction when the needle shield 1.1 is displacedwith respect to the support body 1.2 in the proximal direction, wherebythe resilient arm 1.1.2 disengages the catching recess 1.2.3 to releasethe needle shield 1.1.

FIGS. 11A and 11B show two cross-sections of the needle shield 1.1according to third embodiment of the invention. The sectional viewsshown in FIGS. 11A and 11B extend perpendicular to the central axis A ofthe safety device 1.

As can be seen in FIG. 11A, the retention and locking means M comprisetwo resilient arms 1.1.2 arranged opposite each other. The resilientarms 1.1.2 are in a mechanically unstressed state and latch to thecatching recess 1.2.3. According to the third embodiment, the retentionand locking means M comprises two interlocking elements 1.1.4respectively arranged in the area between the two resilient arms 1.1.2.

The interlocking elements 1.1.4 are arranged opposite to each other andact as means to lock the two resilient arms 1.1.2 to each other when theresilient arms 1.1.2 are deflected in the radial inward direction afterthe resilient arms 1.1.2 engaged the second ramp 1.2.7, as illustratedin FIG. 11B. The inwardly deflected and stressed resilient arms 1.1.2latch to the interjacent interlocking elements 1.1.4, so that thedeflected resilient arms 1.1.2 are retained in an inwardly deflectedposition and locked together. The two interlocking elements 1.1.4 andthe two resilient arms 1.1.2 form an essentially ring-shaped interlockedstructure S.

FIG. 12 shows a sectional view of the injection device D according tothe third embodiment of the invention with the needle shield 1.1positioned in the retracted position PR.

The spring arm 1.4.1 engages the first ramp 1.2.6 and is deflected inthe radial outward direction. The spring arm 1.4.1 is stressed andbiases the needle shield 1.1 in the distal direction.

The resilient arm 1.1.2 engages the second ramp 1.1.2 arranged at thedistal end of the support body 1.2. The second ramp 1.2.7 pushes theresilient arm 1.1.2 radial inwardly, so that the deflected resilient arm1.1.2 is oriented with respect to the central axis A at an acute angle.

FIG. 13 shows the injection device D according to third embodiment ofthe invention after the dose of the medicament contained in the innercavity 2.3.2 of the pre-filled syringe 2 has been administered to thepatient. The support body 1.2 is substantially received within the outerbody 1.3 and the stopper 2.4 is fully depressed in the inner cavity2.3.2.

FIG. 14 shows the injection device D according to the third embodimentof the invention in the needle safe state. The needle shield 1.1 islocked to the second advanced position PA2 and surrounds the injectionneedle 2.1 to prevent accidental needle stick injuries.

The catch 1.2.2 formed to the distal end of the support body 1.2 latchesto the second inward projection 1.2.5 connected to the needle shield 1.1to permanently lock the needle shield 1.1 to the second advancedposition PA2, so that a re-exposure of the injection needle 2.1 isprevented.

FIG. 15 shows a sectional view of an injection device D according to aforth embodiment of the invention. The forth embodiment represents oneof many possible examples of injection devices D that are within thescope of the present invention and can be viewed as a particularlyadvantageous combination of the second and the third embodiment alreadydescribed herein above.

In particular, the injection device D according to the forth embodimentis similar in outer appearance to the injection device D of the secondembodiment and comprises the needle shield 1.1 of particular compactdesign. The retaining and locking means M are designed similar to theinjection device D of the third embodiment and comprise two inwardlydeflectable resilient arms 1.1.2 that may be locked to each other viainterjacent locking elements 1.1.4 to form the interlocked structure Swith essentially ring-shaped cross-section as illustrated in detail inFIGS. 11A and 11B.

The injection device D according to the third and forth embodiment ofthe invention is essentially used during an injection as describedherein above. In particular, a possible sequence of actions include theremoval of the needle cap 2.2 from the distal tip of the barrel 2.3, thearrangement of the injection device D at the injection site in manner,so that the annular flange 1.1.1 rests onto the skin of the patient,gripping the outer body 1.3 and pushing the outer body 1.3 towards theskin surface, whereby the needle shroud 1.1 first moves from the firstadvanced position PA1 to the retracted position PR before the outer body1.3 is translated in the distal direction to inject the dose of themedicament. After the injection device D is taken away from theinjection site, the spring means 1.4 relaxes and moves to the secondadvanced position PA2.

FIGS. 16A to 16D illustrate in detail the retention and locking means Maccording to the third and forth embodiment of the invention.

Before the injection, the needle shield 1.1 is initially retained in thefirst advanced position PA1 shown in FIG. 16A. The needle shield 1.1 isreleasably retained in the first advanced position PA1 by the retainingarm 1.1.2 engaging the catching recess 1.2.3, wherein the retaining arm1.1.2 is not mechanically stressed and extends essentially parallel tothe central axis A. The needle shield 1.1 is released by a lineartranslation parallel to the central axis A in the proximal direction,whereby the second ramp 1.2.7 abuts and deflects the resilient arm 1.1.2in the radial inward direction, as illustrated in FIG. 16B. The twodeflected resilient arms 1.1.2 latch to the interlocking elements 1.1.4to form the interlocked structure S as illustrated in FIG. 11B.

During the injection, the needle shield 1.1 moves further in theproximal direction until the needle shield 1.1 reaches the retractedposition PR shown in FIG. 16C. The injection needle 2.1 protrudes theannular flange 1.1.1 resting on the skin of the patient and puncturesthe skin of the patient. After the dose of the medicament is disposedbeneath the skin of the patient, the injection device is removed fromthe skin. The spring means 1.4 relaxes and pushes the needle shield 1.1distally to surround the used injection needle 2.1 in the secondadvanced position PA2. The needle shield 1.1 is permanently locked tothe advanced position PA2 to prevent needle stick injuries after use ofthe injection device D.

FIGS. 17A to 17D illustrate possible arrangements of a resilient arm1.2.3 retaining the needle shield 1.1 relative to the support body 1.2within the scope of the present invention.

FIG. 17B shows an arrangement of the resilient arm 1.1.2 formed to theneedle shield 1.1. The resilient arm 1.1.2 is deflected in the radialinward direction to latch to the catching recess 1.2.3 formed into thedistal end of the support body 1.1, so that the needle shield 1.1 isinitially retained in the first advanced position PA1.

FIG. 17C shows an arrangement of the resilient arm 1.1.2 formed to thedistal end of the support body 1.2. The resilient arm 1.1.2 is deflectedin the radial inward direction to latch to the catching recess 1.2.3formed into the needle shield 1.1, so that the needle shield 1.1 isinitially retained in the first advanced position PA1.

FIG. 17D shows an arrangement of the resilient arm 1.1.2 formed to thedistal end of the support body 1.2. The resilient arm 1.1.2 is deflectedin the radial outward direction to latch to the catching recess 1.2.3formed the needle shield 1.1, so that the needle shield 1.1 is initiallyretained in the first advanced position PA1.

The invention claimed is:
 1. A safety device for a pre-filled syringewith an injection needle, the safety device comprising: a support bodyadapted to receive the pre-filled syringe; a needle shield slidablyarranged with respect to the support body; a retention and lockingmechanism (M) configured to releasably retain the needle shield withrespect to the support body in a first advanced position (PA1) and lockthe needle shield with respect to the support body in a second advancedposition (PA2); wherein the retention and locking mechanism (M) isgenerally arranged distally within the safety device, and wherein theneedle shield in the first advanced position (PA1) protrudes from thesupport body in a distal direction by a first distance (D1) and theneedle shield in the second advanced position (PA2) protrudes from thesupport body in the distal direction by a second distance (D2), whereinthe first distance (D1) is smaller than the second distance (D2).
 2. Thesafety device according to claim 1, wherein the retention and lockingmechanism (M) is configured to release the needle shield from the firstadvanced position (PA1) by a linear movement of the needle shield withrespect to the support body.
 3. The safety device according to claim 1,wherein the retention and locking mechanism (M) comprise at least onedeflectable resilient arm.
 4. The safety device according to claim 3,wherein the at least one deflectable resilient arm is arranged with theneedle shield as one piece.
 5. The safety device according to claim 3,wherein the at least one deflectable resilient arm latches to a recessformed in a distal region of the support body.
 6. The safety deviceaccording to claim 5, wherein the at least one deflectable resilient armlatches to the recess to retain the needle shield in the second advancedposition (PA2).
 7. The safety device according to claim 5, wherein theat least one deflectable resilient arm is deflected in a radial inwarddirection and subsequently unbends when latching to the recess.
 8. Thesafety device according to claim 3, wherein the at least one deflectableresilient arm comprises two inwardly deflectable resilient arms that arearranged opposite to each other.
 9. The safety device according to claim1, wherein the needle shield is biased with respect to the support bodyin the distal direction by a spring.
 10. The safety device according toclaim 9, wherein the spring comprises a distal end which bears against acollar arranged on the needle shield.
 11. The safety device according toclaim 9, wherein the spring comprises a proximal end which bears againstthe support body.
 12. The safety device according to claim 1, whereinthe retention and locking mechanism (M) and the needle shield areconfigured to interact with each other at a distal end of the safetydevice.
 13. The safety device according to claim 12, wherein theretention and locking mechanism (M) comprises a recess arranged at thedistal end of the safety device, the recess configured to releasablyretain the needle shield at the distal end of the safety device.
 14. Thesafety device according to claim 1, wherein a portion of the needleshield is supported within the support body.
 15. The safety deviceaccording to claim 14, wherein the portion of the needle shieldsupported within the support body comprises at least one deflectableresilient arm.
 16. An injection device comprising: a pre-filled syringe;and a safety device comprising: a support body adapted to mount thepre-filled syringe; a needle shield slidably arranged with respect tothe support body; a retention and locking mechanism (M) configured toretain and lock the needle shield with respect to the support body in afirst advanced position (PA1) and a second advanced position (PA2);wherein the needle shield comprises an annular flange adapted to rest onan injection site, wherein the retention and locking mechanism (M) arearranged at a distal end of the safety device, and wherein the needleshield is movable from the first advanced position (PA1) to a retractedposition (PR) and further to the second advanced position (PA2), whereinthe needle shield in the first advanced position (PAT) protrudes thesupport body in a distal direction by a first distance (D1) and theneedle shield in the second advanced position (PA2) protrudes thesupport body in the distal direction by a second distance (D2), whereinthe first distance (D1) is smaller than the second distance (D2). 17.The injection device of claim 16, wherein the pre-filled syringecontains a drug containing at least one pharmaceutically activecompound.